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Experimental cancer pharmaceuticals under trial
Date:10/23/2007

A potent and selective inhibitor of the mitotic kinesin CENP-E (GSK923295A) demonstrates a novel mechanism of inhibiting tumor cell proliferation and shows activity against a broad panel of human tumor cell lines in vitro: Abstract A 111.

A first-in-class, targeted investigational therapy specifically designed to inhibit a single protein that functions only during cell division shows potent activity in a broad range of cancer cell lines, say researchers from GlaxoSmithKline. Because the compound is so specifically targeted, it may help reduce some of the more common toxic side effects of chemotherapy, they say.

The experimental drug, GSK923295A, inhibits the mitotic kinesin centromere-associated protein E (CENP-E), which is required during mitosis, the process by which a cell duplicates its genetic information in order to generate two, identical, daughter cells. The resulting mitotic arrest can lead to apoptosis, or cell death. A characteristic of CENP-E inhibition is the presence of misaligned or lagging chromosomes within cells attempting to replicate.

Investigators were able to observe lagging chromosomes in most tumor cells treated with GSK923295A. These effects are rarely observed in untreated cells, said the studys lead investigator, David Sutton, B.Sc., associate director of biology, within the Oncology division of GlaxoSmithKline in Collegeville, Pa. GlaxoSmithKline funded the study.

Although CENP-E is expressed in all dividing cells, GSK923925A is more likely to affect rapidly dividing cancer cells, Sutton says. Furthermore, because of the very low expression of CENP-E in non-dividing cells such as neurons, GSK923295A may not cause the peripheral nerve damage often seen with chemotherapy treatments such as taxanes and vinca alkaloids, which also inhibit mitosis, he says.

Studies conducted in animal models have shown complete tumor regression in some cancer types, says Sutton. In preclinical tests conduc
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Contact: Greg Lester
greg.lester@aacr.org
267-646-0554
American Association for Cancer Research
Source:Eurekalert

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